Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer

Yiran Zhang,Ranlu Liu,Qingqing Huang,Yanming Wang,Yueqi Zhu,Yingsheng Cheng,Li Meng,Wenguo Cui

doi:10.1186/s12951-020-00756-6

Abstract

BackgroundChemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA.ResultsThe particle size of the micelles was 42 nm, the zeta potential increased from − 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation.ConclusionsThis targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.

Highlights

Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer
An 18-month endocrine therapy often causes the disease to progress to castration-resistant prostate cancer (CRPC), and androgen deprivation therapy (ADT) generally loses its efficacy
The gel permeation chromatography (GPC) chromatograms showed a sharp peak at 16 min with a PDI of 1.12, which indicated a molecular weight of 33,161 g/mol and a uniform product

Summary

Introduction

Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. Prostate cancer (PCa) is a disease that has been reported worldwide and has become the most frequently diagnosed cancer. In 2019, newly diagnosed PCa cases were estimated at 174,650 (20% of male cancers) with 31,620. The incidence rates of PCa remained the highest of all male cancers from 1975 to 2015 [1]. The current treatment strategy includes surgical treatment, endocrine therapy, immunotherapy, gene therapy and chemotherapy [2]. An 18-month endocrine therapy often causes the disease to progress to castration-resistant prostate cancer (CRPC), and androgen deprivation therapy (ADT) generally loses its efficacy. Immunotherapy is generally expensive or lacks universality; chemotherapy and gene therapy have become the ultimate treatments for such patients

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